Ingestible Oral Care Compositions and Uses Thereof

Abstract

The present disclosure relates to ingestible oral care compositions and their use, for example, to control dental plaque and / or gingival inflammation in a subject. For example, the ingestible oral care composition may include: proteins, lipids, polysaccharides and / or derivatives thereof, and optionally active agents, in a water-based, orally acceptable vehicle.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This disclosure claims the benefit of priority from co-pending U.S. Provisional Application No. 63 / 436,529, filed December 31, 2022, the contents of which are incorporated herein by reference in their entirety.

[0002] Field The present disclosure relates to ingestible oral care compositions and their uses, for example, to control dental plaque and / or gum inflammation in a subject. [Background technology]

[0003] background Dental plaque is a sticky film that covers teeth and contains bacteria. It is associated with common dental diseases, particularly caries and gingival disease. Recent studies have also shown that plaque infection may contribute to systemic inflammation. Dental plaque is a biofilm composed of microorganisms distributed in an intercellular matrix. The matrix is ​​primarily composed of organic components: polysaccharides, proteins, glycoproteins, and lipids; inorganic components: calcium, phosphorus, sodium, potassium, and fluoride. Exopolysaccharides produced by bacteria comprise 50–95% of the dry weight of the plaque biofilm. These components contribute to the structural integrity of the biofilm and its attachment to tooth surfaces.

[0004] Approximately 50% of the adult population worldwide is affected by gingivitis. Gingivitis and periodontitis are the same inflammatory continuum, and not all patients with gingivitis progress to periodontitis. Gingivitis management is both a primary prevention strategy for periodontitis and a secondary prevention strategy for recurrent periodontitis. The most important risk factor for gingivitis and periodontitis is the accumulation of plaque biofilm at and below the gingival margin, in which dysbiosis develops and is associated with an inappropriate and destructive host inflammatory immune response. Therefore, oral care products that can be applied topically to gingival tissues to control gingival inflammation, prevent gingivitis, and / or prevent gingivitis from progressing to periodontitis would be desirable for managing periodontal disease.

[0005] Daily brushing, flossing, and the use of antibacterial mouthwashes are commonly recommended measures for controlling plaque accumulation. While these measures may provide temporary removal and / or control of biofilms, they cannot completely remove them. Furthermore, frequent mechanical interventions, if not properly controlled, can lead to harmful effects on the soft tissues surrounding the teeth and may contribute to gingival recession, especially in elderly people. While dental plaque can be controlled by these measures, due to the dynamic interactions between the host and microbiome community, food, and / or the stresses of modern life, there is a need for non-invasive adjunctive measures to soothe soft tissues after mechanical intervention, maintain oral microbiota homeostasis, and help prevent biofilm-induced pathogenicity and / or inflammation. Oral care products that are safe and convenient for daily use and provide longer and more effective protection of gums and teeth from biofilm growth and dysbiosis would complement current oral care regimens and potentially provide improved maintenance and enhancement of oral health and potentially the overall health associated with oral health. However, the moist environment and dynamic functions of the mouth can pose significant challenges for left-in oral care products. Another challenge for ingestible oral care products is the potential for plaque regrowth (see, e.g., Rubido et al., In vivo antiplaque effect of three edible toothpastes Med Oral Patol Oral Cir Bucal. 2014 Jan 1;19(1):e88-92). Summary of the Invention

[0006] overview Briefly, the present disclosure comprises methods and compositions for application to dental and gingival surfaces that persist on contact surfaces for extended periods of time and are safe for ingestion after application. Surprisingly, the highly biocompatible disclosed ingestible oral compositions controlled plaque regrowth and accumulation in a non-invasive manner without mechanical force or antimicrobial chemicals.

[0007] When applied to the tooth surface, the exemplary ingestible oral care composition of the present disclosure attached to the existing biofilm altered the cohesiveness of the EPM and reduced the mechanical stability of the matrix, while at the same time acting as a physical barrier to prevent further bacterial adhesion to the existing biofilm. Without wishing to be limited by theory, this highly biocompatible composite appears to act like a camouflage for oral biofilms, weakening biofilm growth and preserving the biofilm at a level compatible with oral health by destabilizing the existing biofilm and diverting its growth.

[0008] The present disclosure includes ingestible oral care compositions comprising a protein; a lipid; a polysaccharide and / or derivatives thereof; and optionally an active agent in a water-based, orally acceptable vehicle.

[0009] In one embodiment, the ingestible oral care composition further comprises a pH neutralizing agent.In one embodiment, the ingestible oral care composition comprises an active agent.

[0010] The present disclosure also includes the use of the ingestible oral care composition described herein for controlling gingival inflammation in a subject.The present disclosure also includes the use of the ingestible oral care composition described herein, which comprises an active substance, for controlling respiratory diseases through the mouth and throat in a subject.The present disclosure also includes the use of the ingestible oral care composition described herein for preventing systemic diseases associated with periodontal inflammation in a subject.The present disclosure also includes the use of the ingestible oral care composition described herein for non-invasively destabilizing plaque, preventing plaque regrowth, and / or reducing plaque on the oral surface of a subject.The present disclosure also includes the use of the ingestible oral care composition described herein, which comprises an active substance, for delivering the active substance to a subject in need thereof.

[0011] Specific embodiments of the present disclosure are: a) brushing the product over the entire tooth and gum surfaces using a soft toothbrush and leaving it to slowly disperse in the oral cavity, preferably at night after regular tooth cleaning with toothpaste and dental floss, where the brushing and leaving oral care product acts as a leave in conditioning agent after tooth cleaning, an easy and convenient supplement to current oral care regimen; b) whenever necessary, with or without the aid of clean dental floss to push the product further into the tooth roots or periodontal pockets for maximum effect on specific targeted tooth and gum surfaces, i.e., pain, bleeding, sensitivity, swelling, gingiva inflammation. , gum recession, etc.; c) applying the product to targeted spots on the surface of the teeth and gums, or to the base of specific teeth or specific periodontal pockets, directly by hand, or with a brush, or with the aid of clean dental floss, or with a specific dental product application tool such as a curved-tip syringe for therapeutic purposes, as a medicinal application, in which a therapeutic agent suitable for topical application is carried in the product; d) including, but not limited to, health-promoting ingredients or drugs that provide additional benefits for general health or, in particular, respiratory health through regular use of the product, enabled by prolonged release and ingestion after application. The aforementioned extended period of contact on the surface of the teeth and gums allows for a longer local delivery time and creates opportunities for more efficient delivery and a safer long-term profile of the health-promoting ingredients or drugs.

[0012] Exemplary oral care products suitable for use in the aforementioned methods may include a base, including but not limited to the following materials: polysaccharides and polysaccharide derivatives, proteins, and lipids, in an orally acceptable vehicle containing humectants, sweeteners, flavoring agents, buffers, water, and / or preservatives. Application of the base alone inhibits plaque accumulation and prevents caries and periodontal disease. In another embodiment, the ingestible oral care composition further includes one or more pH neutralizing agents, such as inorganic salts, which may, for example, neutralize acid in situ and / or further prevent caries. In another embodiment, the oral composition further includes one or more oral health-promoting actives, including but not limited to antioxidants, anti-inflammatory agents, antimicrobial agents, nutrients, sensates, botanical extracts, essential oils, and the like, for the management of local pain, sensitivity, ingival inflammation, swollen gums, bleeding gums, receding gums, malodor, and the like, or potentially for the control of systemic or respiratory health concerns. The oral compositions, in another embodiment, carry drug actives in a vehicle for targeted local delivery to the tooth roots and / or periodontal pockets as a safe and effective treatment option for gum disease.

[0013] Other features and advantages of the present disclosure will become apparent from the following detailed description. However, it should be understood that the detailed description and specific examples, while indicating embodiments of the disclosure, are given by way of illustration only, and that the scope of the claims should not be limited by these embodiments, but rather should be accorded the broadest interpretation consistent with the description as a whole. [Brief explanation of the drawings]

[0014] [Figure 1] FIG. 1 is a plot showing a comparison between stained bacterial counts for samples taken from the oral cavity of subjects to which an ingestible oral care composition according to an embodiment of the present disclosure was applied (left column) compared to a control (right column) for samples taken from left to right at 0, 15, 30, 60, 90 and 120 minutes. DETAILED DESCRIPTION OF THE INVENTION

[0015] Detailed Description I. Definition Unless otherwise indicated, the definitions and embodiments set forth in this and other sections are intended to be applicable to all embodiments and aspects of the disclosure described herein as they would be understood to be appropriate by one of ordinary skill in the art.

[0016] As used herein, the words "comprising" (and any form of "comprising," such as "comprise" and "comprises"), "having" (and any form of "having," such as "have" and "has"), "including" (and any form of "including," such as "include" and "includes"), or "containing" (and any form of "containing," such as "contain" and "contains") are inclusive or open-ended and do not exclude additional, unrecited elements or process / method steps. As used herein, the word "consisting" and its derivatives are intended to be close-ended terms specifying the presence of stated features, elements, components, groups, integers, and / or steps, and also excluding the presence of other, unrecited features, elements, components, groups, integers, and / or steps. As used herein, the term "consisting essentially of" is intended to specify the presence of stated features, elements, components, groups, integers, and / or steps, and other things that do not materially affect the basic and novel characteristic(s) of those features, elements, components, groups, integers, and / or steps.

[0017] As used herein, terms of degree, such as "substantially," "about," and "approximately," refer to a reasonable amount of deviation from the modified term so that the end result does not change significantly. These terms of degree should be interpreted as including a deviation of at least ±5% of the modified term, provided that this deviation would not negate the meaning of the word it modifies.

[0018] As used in this disclosure, the singular forms "a," "an," and "the" include plural references unless the content clearly dictates otherwise.

[0019] As used herein, the term "and / or" means that the listed items are present or used either individually or in any combination. In effect, the term means that "at least one" or "one or more" of the listed items are used or present.

[0020] By "ingestible," it is meant, for example, that the components of the product / composition, particularly the components in the base, are considered suitable for consumption by a subject at the levels used in the disclosed product / composition; for example, they may be materials generally regarded as safe (GRAS) by the U.S. Food and Drug Administration (FDA) and / or food-grade, while the additional active substance may be, for example, a GRAS material, a food-grade material, and / or otherwise used at levels suitable for daily oral intake. In embodiments in which the active substance comprises a pharmaceutically active compound, it will be recognized by those skilled in the art that such active substance is desirably present in a form compatible with treatment of a subject, for example, via delivery through an ingestible oral care composition, and for administration / use in a subject in an effective amount, at dosages and for periods of time necessary to achieve the desired result. That is, the disclosed product / ingestible oral care composition is suitable for leaving in the oral cavity, for example, after daily application, or after multiple applications within a day, or as prescribed depending on the embodiment. The disclosed ingestible oral care compositions may therefore advantageously act on teeth and gum surfaces for extended periods of time, for example, as a leave in oral care product to destabilize plaque, prevent plaque regrowth, and / or non-invasively reduce plaque. Alternatively, in some embodiments, the ingestible oral care compositions are for temporary therapeutic use.

[0021] As used herein, the term "non-invasively" and the like means, for example, without significant mechanical force, brushing and / or application of antimicrobial chemicals.

[0022] By " long-lasting ", it means that after applying the product on the surface of teeth and gums, the product remains on these surfaces for 10 minutes or longer.The length of retention time is affected by the oral activity after application.In one embodiment, the longer retention time is achieved by using a soft brush to apply the product to the entire surface of teeth and gums after cleaning teeth with toothpaste and / or floss before going to bed at night.

[0023] By "attractive mouthfeel and convenient application method," it is meant that the consistency and texture of the product are semi-solid in nature, similar to that of commercially available toothpaste. The product can be packed in the same way as toothpaste or in a different way. The product can also be brushed with a toothbrush on the gums and tooth surfaces, preferably with gentle movements using a soft toothbrush, to cover all surface areas. The product applied in this way is essentially a gel and subsequently does not leave any solid residue in the mouth over time, but preferably has a pleasant and refreshing flavor embedded in the product, and dissolves and disperses in the oral cavity. A product applied in this way can be easily added to the current daily oral care routine after toothpaste and flossing as a supplemental leave-in in the teeth and gum conditioning step, which utilizes functional oral care actives in a safer and more effective way than when they are used in toothpaste or mouthwash, while the actives are expelled or washed out of the mouth after only a short contact time.

[0024] As used herein, the term "oral surface" includes any surface in the mouth suitable for application thereon of an ingestible oral care composition, such as suitable mucosal surfaces (e.g., gums), natural teeth, artificial teeth (e.g., implants), and teeth having dental restorations thereon (e.g., crowns or bridges), and combinations thereof.

[0025] II. Ingestible Oral Care Compositions and Their Uses The present disclosure includes oral care products comprising a base composed of the following: polysaccharides and / or polysaccharide derivatives, proteins, lipids, in an orally acceptable vehicle containing humectants, sweeteners, flavoring agents, buffers, water, and / or preservatives. In these oral care products, carefully selected polysaccharides and / or polysaccharide derivatives, proteins, and lipids, which are either part of natural biofilm compositions or specific highly biocompatible substitutes, and optionally inorganic salts are combined with, for example, humectants, sweeteners, flavoring agents, and water to prepare the product with a consistency and texture that can be easily applied to a topical surface and remain there for a period of time before being fully dispersed throughout the oral cavity, while also adhering to the surface of teeth and gums. Once the product is applied to a topical surface after a tooth cleaning procedure, its retention on the topical surface destabilizes residual plaque, forming a physical barrier that would otherwise delay the recurrence of biofilm formation on the tooth surface, and further reducing the likelihood of plaque formation and accumulation on the tooth surface. Optionally, inorganic salts are included in the product to neutralize acids in situ, which further prevents tooth decay and reduces gum inflammation and associated local bleeding and / or swelling. Optionally, an active agent is included for local delivery.

[0026] The present disclosure also includes ingestible oral care compositions comprising polysaccharides and / or derivatives thereof; proteins; lipids; inorganic salt pH neutralizers; humectants; sweeteners; flavorings; water; and optionally, active substances. The present disclosure also includes ingestible oral care compositions comprising proteins; lipids; polysaccharides and / or derivatives thereof; water; and optionally, inorganic salt pH neutralizers; humectants; sweeteners; flavorings; and / or active substances.

[0027] The present disclosure also includes ingestible oral care compositions comprising a protein; a lipid; a polysaccharide and / or derivatives thereof; and optionally an active agent in a water-based, orally acceptable vehicle.

[0028] The protein may be any suitable protein or combination thereof and may be present in any suitable amount. In one embodiment, the protein is present in an amount of about 0.05% to about 10% by weight based on the total weight of the ingestible oral care composition. In another embodiment, the protein is present in an amount of about 0.1% to about 5% by weight based on the total weight of the ingestible oral care composition. The protein in the above-mentioned product includes, but is not limited to, collagen, gelatin, soy protein, pea protein, and proline-rich proteins, particularly for adhesion to tooth surfaces. Therefore, those skilled in the art will readily recognize that the term "protein" as used herein also includes suitable materials derived from proteins, such as, but not limited to, gelatin and / or hydrolyzed collagen, as well as materials containing suitable mixtures of proteins, such as, but not limited to, soy protein, pea protein, rice protein, and / or whey protein. In one embodiment, the protein is a proline-rich protein. In one embodiment, the protein is gelatin, hydrolyzed collagen, pea protein, soy protein, rice protein, whey protein, or a combination thereof. In another embodiment, the protein is selected from collagen, gelatin, soy protein, pea protein, and combinations thereof. In one embodiment, the protein is a combination of hydrolyzed collagen and gelatin. Gelatin is a preferred choice due to its high biocompatibility and its potential to prevent gum recession and enhance gum healing, regrowth, and tooth attachment. In one embodiment, the protein is gelatin. In a further embodiment, gelatin is present in an amount of 0.1% to about 5% by weight based on the total weight of the ingestible oral care composition.

[0029] The polysaccharide and / or its derivative may be any suitable polysaccharide, polysaccharide derivative, or combination thereof, and may be present in any suitable amount. In one embodiment, the polysaccharide and / or its derivative is present in an amount of about 0.3% to about 42% by weight based on the total weight of the ingestible oral care composition. In one embodiment, the polysaccharide and / or its derivative is present in an amount of about 1.6% to about 27% by weight based on the total weight of the ingestible oral care composition. The polysaccharides and / or polysaccharide derivatives in the aforementioned products include, but are not limited to, plant-based materials such as cellulose and cellulose derivatives, pectin, acacia gum, gum arabic, inulin, guar gum, tara gum, and locust bean gum; animal-derived materials such as hyaluronic acid, sodium hyaluronate, chitin, chitosan, and heparin; microbial-based materials such as pullulan, xanthan gum, gellan gum, and succinoglycan; and algae-based materials such as alginate, agar, carrageenan, and fucoidan. In one embodiment, the polysaccharides and / or their derivatives are selected from plant-based materials, animal-based materials, microbial-based materials, algae-based materials, and combinations thereof. In another embodiment, the polysaccharides and / or their derivatives are selected from cellulose, cellulose derivatives, pectin, acacia gum, arabinogalactan-containing gum, gum arabic, inulin, guar gum, tara gum, locust bean gum, hyaluronic acid, sodium hyaluronate, chitin, chitosan, heparin, pullulan, xanthan gum, gellan gum, succinoglycan, algin, alginates, agar, carrageenan, fucoidan, and combinations thereof. One or more of the above materials are selected or combined to contribute to the above-mentioned properties, and one preferred option is the combination of pectin, gum arabic, guar gum, xanthan gum, and alginate. Thus, in one embodiment, the polysaccharides and / or their derivatives are the combination of gum arabic, pectin, guar gum, xanthan gum, and sodium alginate.In another embodiment, the polysaccharides and / or derivatives thereof are a combination of arabinogalactan-containing gum, guar gum, xanthan gum, and sodium alginate. The arabinogalactan-containing gum is any suitable arabinogalactan-containing gum or a combination thereof. In one embodiment, the arabinogalactan-containing gum is larch arabinogalactan, ghatti gum, gum arabic, or a combination thereof. In another embodiment, the polysaccharides and / or derivatives thereof are a combination of gum arabic, guar gum, xanthan gum, and sodium alginate. In one embodiment, the arabinogalactan-containing gum is present in an amount of about 0.1% to about 30% by weight, the guar gum is present in an amount of about 0.05% to about 1% by weight, the xanthan gum is present in an amount of about 0.05% to about 1% by weight, and the sodium alginate is present in an amount of about 0.1% to about 10% by weight, based on the total weight of the ingestible oral care composition. In one embodiment, the arabinogalactan-containing gum is gum arabic and is present in an amount of about 1% to about 20% by weight, based on the total weight of the ingestible oral care composition, the guar gum is present in an amount of about 0.05% to about 0.5% by weight, the xanthan gum is present in an amount of about 0.05% to about 0.5% by weight, and the sodium alginate is present in an amount of about 0.5% to about 6% by weight, based on the total weight of the ingestible oral care composition.

[0030] The lipid may be any suitable lipid or combination thereof and may be present in any suitable amount. In one embodiment, the lipid is present in an amount of about 0.2% to about 27% by weight based on the total weight of the ingestible oral care composition. In another embodiment, the lipid is present in an amount of about 1% to about 10% by weight based on the total weight of the ingestible oral care composition. The lipid in the above-mentioned product includes, but is not limited to, medium-chain triglycerides, grapeseed oil, flaxseed oil, avocado oil, coconut oil, sunflower oil, olive oil, sesame oil, etc. The lipid may provide antioxidant and / or anti-inflammatory effects. One preferred option is caprylic / capric triglyceride. Therefore, those skilled in the art will readily recognize that the term "lipid" as used herein also includes suitable combinations of lipids, as well as suitable substances derived from and / or prepared from lipids, such as, but not limited to, caprylic / capric triglyceride. In one embodiment, the lipid is a medium chain triglyceride, grapeseed oil, flaxseed oil, avocado oil, coconut oil, palm oil, sunflower oil, olive oil, sesame oil, or a combination thereof. In another embodiment, the lipid is caprylic / capric triglyceride. In another embodiment, the caprylic / capric triglyceride is present in an amount of about 1% to about 10% by weight, based on the total weight of the ingestible oral care composition.

[0031] In one embodiment, the ingestible oral care composition further comprises a pH neutralizing agent. In one embodiment, the pH neutralizing agent is an inorganic salt pH neutralizing agent. The inorganic salt may be any suitable inorganic salt or combination thereof that can act as a pH neutralizing agent in the ingestible oral care composition, and may be present in any suitable amount. For example, in the disclosed orally ingestible oral care compositions, the pH neutralizing agent advantageously neutralizes acids in situ for an extended period of time, which may prevent, for example, caries and / or tooth decay. In one embodiment, the pH neutralizing agent is present in an amount of about 0.2% to about 3% by weight, based on the total weight of the ingestible oral care composition. The inorganic salts in the aforementioned products include, but are not limited to: dicalcium phosphate dihydrate, anhydrous dicalcium phosphate, and tricalcium phosphate. Thus, in one embodiment, the pH neutralizing agent is anhydrous dicalcium phosphate, dicalcium phosphate dihydrate, tricalcium phosphate, or a combination thereof. The inorganic salt is a fine powder that is non-abrasive and has limited solubility in water. Once applied, the salt powder embedded in the product resides on the tooth and gum surfaces, continuously neutralizing local acid and maintaining a neutral pH level to prevent erosion and caries on the tooth surface, inhibit plaque accumulation, and prevent gum disease. The combination of the above salts in a specific ratio can also provide a pH-adjusting function so that the overall pH of the aforementioned product is between 6.5 and 7.5. One preferred option is a combination of anhydrous dicalcium phosphate and tricalcium phosphate with fine particle size. Thus, in one embodiment, the ingestible oral care composition includes a combination of anhydrous dicalcium phosphate and tricalcium phosphate.

[0032] Those skilled in the art will recognize that water-based orally acceptable vehicle can contain, in addition to water, one or more components selected from, for example, buffering agent, humectant, sweetener, flavoring agent and preservative.The water-based orally acceptable vehicle can be present in any suitable amount to achieve desired product, and its determination can be made by those skilled in the art.For example, those skilled in the art will recognize that the disclosed ingestible oral care composition is not in the form of a film, but rather in the form of a semi-solid, such as gel.

[0033] The buffering agent may be any suitable buffering agent or combination thereof, and may be present in any suitable amount.In one embodiment, the buffering agent is trisodium phosphate, sodium citrate, citric acid, and sodium hydroxide, or a combination thereof.In another embodiment, the buffering agent is a combination of sodium citrate, citric acid, and sodium hydroxide.For example, in contrast to the pH neutralizing agent used to have a neutralizing effect when applied to the oral surface of a subject, the buffering agent and its amount are selected to have an effect on the disclosed product / ingestible oral care composition.In one embodiment, the buffering agent is present in an amount of about 0.1% by weight to about 1% by weight, based on the total weight of the ingestible oral care composition.

[0034] The humectant may be any suitable humectant or combination thereof, and may be present in any suitable amount. The humectant in the product includes, but is not limited to, glycerin, propylene glycol, butylene glycol, propanediol, pentylene glycol, and other organic humectants, such as aloe vera. The humectant retains water in the product, contributes to the formation of a semi-solid structure, and prevents microbial growth in the product. One preferred option is the combination of glycerin with aloe vera due to the soothing properties of aloe vera. Thus, in one embodiment, the humectant is a combination of glycerin and aloe vera. In another embodiment, the humectant comprises, consists essentially of, or consists of glycerin. In a further embodiment, the humectant comprises glycerin.

[0035] The sweetener may be any suitable sweetener or combination thereof, and may be present in any suitable amount. The sweetener in the above-mentioned product includes, but is not limited to, sugar alcohols such as xylitol, erythritol, sorbitol, and other sugar substitutes such as pure stevia, monk fruit extract, acesulfame potassium, advantame, aspartame, neotame, saccharin, and sucralose, among which low / zero calorie sweeteners such as erythritol and xylitol are preferred due to their well-established advantages for use in oral care products. In one embodiment, the sweetener is selected from sugar alcohols, other sugar substitutes, and combinations thereof. In another embodiment, the sweetener is selected from xylitol, erythritol, sorbitol, pure stevia, monk fruit extract, acesulfame potassium, advantame, aspartame, neotame, saccharin, and sucralose. Erythritol and / or a combination of erythritol and xylitol are preferred options for the product. In one embodiment, the sweetener is erythritol and / or a combination of erythritol and xylitol. In another embodiment, the sweetener comprises, consists essentially of, or consists of xylitol. In a further embodiment, the sweetener comprises xylitol.

[0036] The flavoring agent may be any suitable flavoring agent or combination thereof, and may be present in any suitable amount. The flavoring agent in the above-described product includes, but is not limited to, peppermint and spearmint. A preferred flavoring agent is a mint flavoring agent, including one or both of peppermint and spearmint. Thus, in one embodiment, the flavoring agent is a mint flavoring agent. In another embodiment, the flavoring agent is peppermint, spearmint, or a combination thereof.

[0037] Here, the ingredients in the aforementioned product, when properly combined with water, not only provide the aforementioned properties to the base, but also, upon application, provide a tooth-friendly microbiome environment, support the diversity of the oral microbiome, and inhibit the overgrowth of acidogenic and / or pathogenic microbiomes. In one embodiment, the correct combination of the aforementioned preferred options for each component includes a specific ratio of each ingredient, a specific mixing condition, and an order of addition at a temperature, which, when optimized, can achieve the physical and chemical properties described above. However, those skilled in the art will recognize that the product / composition can be easily prepared using methods common in the oral product field and will be able to easily select an appropriate method.

[0038] In some embodiments, the product / composition includes an active agent. The active agent can thus be delivered to the oral cavity through the disclosed ingestible oral care composition. The active agent can be any suitable active agent or combination thereof and can be present in any suitable amount, which can depend, for example, on the identity of the active agent or combination thereof. Active agents with specific health-promoting functions and compatible physical and chemical properties, such as pH, solubility, and stability with the base, can be embedded in a manner simple to those skilled in the art. These active agents can advantageously be used at relatively lower concentrations, but exert their function locally on targets on the surfaces of the teeth and gums to reduce plaque, control gingivitis, prevent periodontitis, and prevent dental caries for an extended period of time, potentially producing greater efficacy and a better long-term safety profile. The active agents include, but are not limited to, antioxidants, anti-inflammatory agents, antibacterial agents, nutrients such as vitamins, sensates, plant extracts, essential oils, and the like. In another embodiment, the active agent is selected from antioxidants, anti-inflammatory agents, antibacterial agents, nutrients (such as vitamins), sensates, plant extracts, essential oils, and combinations thereof. In another embodiment, the active substance comprises a vitamin. The vitamin may be any suitable vitamin or a combination thereof. In another embodiment, the vitamin is a combination of vitamin C and vitamin B12. In a further embodiment, vitamin C is present in an amount of about 0.1% to about 2% by weight, and vitamin B12 is present in an amount of about 0.001% to about 0.05% by weight. In another embodiment, the active substance comprises a plant extract. The plant extract may be any plant extract suitable for use in ingestible oral care compositions, or a combination thereof. In another embodiment, the active substance comprises an essential oil. The essential oil may be any essential oil suitable for use in ingestible oral care compositions, or a combination thereof.

[0039] Here, the product having the above-mentioned active substance can be applied as a general conditioning supplement to tooth cleaning treatment as described above, and it can also be applied independently or with other oral treatments to specific points on the surface of teeth and gums, with or without the aid of clean dental floss to further push the product into the roots of teeth and / or periodontal pockets whenever necessary, to alleviate specific dental and / or gum concerns, such as swollen gums, pain, bleeding, sensitivity, bad odor, periodontal inflammation, etc. In some embodiments, provide an oral care product / composition that is safe to ingest and suitable for long-term daily use in the oral cavity, has an attractive mouthfeel and convenient application method.Unlike toothpaste and oral rinse, which then need to be spit out or rinsed away, the product is designed to remain on the surface of teeth and gums in the oral cavity after application.The product slowly disperses in the local environment, thus giving its ingredients a long opportunity to work locally on the surface of teeth and gums. The products are not for cleaning purposes, but to provide better maintenance and protection in the oral cavity, particularly on and / or around the surfaces of the teeth and gums, to prevent caries and reduce periodontal disease through a long-term local presence. The products may contain a semi-solid base and additional active substances that contribute to a specific function locally on and / or around the surfaces of the teeth and gums, as well as possible systemic or respiratory benefits after ingestion.

[0040] The use of the aforementioned base as a drug delivery vehicle for delivering pharmaceutically active substances, particularly to periodontal pockets and surrounding areas, with or without the aid of a curved-tip dental syringe or other fine-tip dental tool, is also a feature included herein. Thus, in one embodiment, the active substance comprises a pharmaceutically active compound. In another embodiment, the active substance comprises a pharmaceutically active compound, a vitamin, a plant extract, an essential oil, or a combination thereof. In a further embodiment, the active substance comprises a pharmaceutically active compound and, optionally, a vitamin, a plant extract, an essential oil, or a combination thereof. Due to the high biocompatibility of the base, the aforementioned drug delivery system can also be applied to similar target areas of teeth with implants, crowns, or bridges, or other natural or artificial teeth after surgery, to control pain and inflammation with minimal side effects. The aforementioned pharmaceutically active substance is preferably compatible with the base in terms of physical and chemical properties, including, but not limited to, pH, solubility, and stability. In another feature included herein, the product includes a substrate and a functional active agent that promotes microbiome balance and / or overall health not only for the oral cavity but also for the respiratory system and / or systemic system with regular use. Examples of the substrate include, but are not limited to, prebiotics such as pectin and / or inulin; examples of the active agent include, but are not limited to, plant extracts such as green tea extract and / or licorice extract.

[0041] The present disclosure also includes the use of the ingestible oral care composition described herein for controlling gingival inflammation in a subject.The present disclosure also includes the use of the ingestible oral care composition described herein for the preparation of a medicament for controlling gingival inflammation in a subject.The present disclosure also includes the ingestible oral care composition described herein for use in controlling gingival inflammation in a subject.The present disclosure also includes a method for controlling gingival inflammation in a subject, comprising applying the ingestible oral care composition described herein to an oral surface of the subject.In one embodiment, the oral surface comprises the gingival surface or a portion thereof.

[0042] The present disclosure also includes the use of an ingestible oral care composition described herein comprising an active substance for controlling respiratory disease through the mouth and throat in a subject.The present disclosure also includes the use of an ingestible oral care composition described herein comprising an active substance for the preparation of a medicament for controlling respiratory disease through the mouth and throat in a subject.The present disclosure also includes an ingestible oral care composition described herein comprising an active substance for use in controlling respiratory disease through the mouth and throat in a subject.The present disclosure also includes a method for controlling respiratory disease through the mouth and throat in a subject in need thereof, comprising applying an ingestible oral care composition described herein comprising an active substance to the oral surface of the subject.

[0043] The present disclosure also includes the use of the ingestible oral care compositions described herein for preventing systemic diseases associated with periodontal inflammation in a subject.The present disclosure also includes the use of the ingestible oral care compositions described herein for the preparation of a medicament for preventing systemic diseases associated with periodontal inflammation in a subject.The present disclosure also includes the ingestible oral care compositions described herein for use in preventing systemic diseases associated with periodontal inflammation in a subject.The present disclosure also includes a method for preventing systemic diseases associated with periodontal inflammation in a subject, comprising applying the ingestible oral care composition described herein to the oral surface of the subject.

[0044] The present disclosure also includes the use of ingestible oral care compositions described herein for non-invasively destabilizing plaque, preventing plaque regrowth and / or reducing plaque on the oral surface of a subject.The present disclosure also includes the ingestible oral care compositions described herein for use in non-invasively destabilizing plaque, preventing plaque regrowth and / or reducing plaque on the oral surface of a subject.The present disclosure also includes the method for non-invasively destabilizing plaque, preventing plaque regrowth and / or reducing plaque on the oral surface of a subject, comprising applying the ingestible oral care compositions described herein to the oral surface of the subject.

[0045] The present disclosure also includes the use of the ingestible oral care composition described herein, comprising the active substance, for delivering the active substance to a subject in need thereof.The present disclosure also includes the use of the ingestible oral care composition described herein, comprising the active substance, for preparing a medicament for delivering the active substance to a subject in need thereof.The present disclosure also includes the ingestible oral care composition described herein, comprising the active substance, for use in delivering the active substance to a subject in need thereof.The present disclosure also includes the method for delivering the active substance to a subject in need thereof, comprising applying the ingestible oral care composition described herein, comprising the active substance, to the oral surface of the subject.

[0046] In one embodiment, the subject is a human.

[0047] The following are non-limiting examples of the present disclosure. [Example]

[0048] Example 1 The disclosed ingestible oral care composition can be prepared using methods commonly used in the oral product field. The ingredients of an exemplary oral care composition are shown in Table 1. In an exemplary procedure for preparing an ingestible oral care composition, gelatin and polysaccharides are first dispersed and hydrated in an orally acceptable vehicle. Surprisingly, medium-chain triglycerides function as a cross-linking agent between proteins and polysaccharides and increase the viscosity of the biopolymer complex base. Once the biopolymer complex base is formed, the remaining pH-neutralizing ingredients, flavors, and active substances are slowly introduced into the base to avoid trapping air. Buffers, sweeteners, flavors, and humectants such as glycerin are introduced into water to form an orally acceptable vehicle.

[0049] [Table 1]

[0050] Gelatin was included due to its biocompatibility and potential as a proline-rich protein that promotes adhesion to tooth surfaces. The first example was prepared using pectin, gum arabic, guar gum, xanthan gum, and alginate. This mixture of polysaccharides was useful for preparing the disclosed ingestible oral care compositions. However, variations in pectin source and inconsistencies in the final mixture led to a focus on four other natural gums.

[0051] A challenge in preparing ingestible oral care products is the local retention of products using ingestible ingredients. The gelatin and polysaccharide mixtures exemplified in Table 1 showed adhesion to tooth surfaces. However, they only remained for a very short time (less than 15 minutes). Surprisingly, when medium-chain triglycerides were added to the gelatin and polysaccharide base, the viscosity increased, the consistency of the base improved, and retention on tooth surfaces increased to nearly 30 minutes. However, it was also found that the amount of medium-chain triglycerides that can be successfully incorporated into the gelatin and polysaccharide base is proportional to other biopolymers. The amounts listed in Table 1 produce gel bases that are applicable as oral care products in compressible containers, and similar ratios are expected to behave similarly.

[0052] Another challenge with ingestible oral care products is the potential for plaque regrowth (see, e.g., Rubido et al., In vivo antiplaque effect of three edible toothpastes Med Oral Patol Oral Cir Bucal. 2014 Jan 1;19(1):e88-92). The effectiveness of individual gum solutions was tested against beta-glucan, a polysaccharide similar to that in EPS. Surprisingly, beta-glucan in gel form disappeared slowly in size in the gum solution, in the following order: gum arabic > alginate > guar gum > xanthan gum. Other arabinogalactan-containing gums similar to gum arabic, highly branched polysaccharides with l-arabinose side chains, were also tested. Larch arabinogalactan and ghatti gum showed similar effects to gum arabic on beta-glucan gel in solution.

[0053] After applying the products of Table 1 to the beta-glucan gel, a similar effect was observed as the beta-glucan gel began to decrease in size. Because beta-glucan is a major component of biofilms, this indicates a potential interaction between the product and biofilm polysaccharides, which could, for example, lead to destabilization and degradation of the biofilm and prevent further plaque growth.

[0054] The product in Table 1 contains gelatin, caprylic / capric triglyceride, and a polysaccharide combination of sodium alginate, gum arabic, xanthan gum, and guar gum. The proteins, lipids, and polysaccharides in the EPM contribute to the biofilm as an energy source, structural component, and communication liaison. All of these molecules are involved in bacterial adhesion to the biofilm and subsequent interactions within the biofilm. Unlike previous products in which polymers or polysaccharides are used as viscous carriers for adhesion to dental surfaces, the polysaccharide combination in this product is not sufficiently viscous to adhere to dental surfaces by itself. Without wishing to be bound by theory, these polysaccharides, particularly sodium alginate and gum arabic, appear to have an antagonistic effect with glucan, the primary component of EPM polysaccharides. Both xanthan gum and guar gum are advantageously used at minimal levels to enhance the final viscoelastic properties of the product, but are not used as viscosity enhancers. Gelatin, as the most biocompatible protein with different hydrophilic (anionic, cationic) and hydrophobic moieties on its amino acid chain, interacts with lipids and polysaccharides as the main structural backbone and helps attach these components to dental biofilms. Medium-chain triglycerides interact similarly with the gelatin and polysaccharide combination, which surprisingly significantly increases the viscosity of the complex, indicating a possible weak cross-linking effect on the complex, without wishing to be limited by theory.

[0055] Example 2 Before collecting samples from the oral cavity, the subjects were asked to brush their teeth with their usual toothpaste for 3 minutes.After brushing their teeth, the subjects applied the oral health care gel product in Table 1 to the surface of the teeth at the gingival margin, and used a soft toothbrush to make it as even as possible and bring it into the gingival sulcus.Samples were collected with an applicator at 0, 15, 30, 60, 90 and 120 minutes.The samples were placed in 1.5 mL vials, and each vial contained 200 μL methylene blue (simple stain) to mix with the sample.Then, 10 μL of the mixed solution was taken into a hemocytometer to count the number of bacteria.Based on the counted number, the number of bacteria in each sample was calculated.

[0056] A reduction in bacteria was observed after application of the gel (Figure 1; n=3).

[0057] Example 3 A 50-year-old healthy female subject applied the oral health care gel product in Table 1 with a soft bristle brush after brushing each night before bed for two weeks. After two weeks of continuous use, signs of controlled gingival recession were observed, as well as a reduction in gingival inflammation.

[0058] While the present disclosure has been described with reference to examples, it should be understood that the scope of the claims should not be limited by the embodiments described in the examples, but should be accorded the broadest interpretation consistent with the description as a whole.

[0059] All publications, patents, and patent applications are herein incorporated by reference in their entirety to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference in its entirety. In the event that a term in this application is found to be defined differently in a document incorporated herein by reference, the definition provided herein shall serve as the definition for that term.

Claims

1. in a water-based orally acceptable vehicle, protein; lipids; Polysaccharides and / or their derivatives; and Optionally, an active substance 1. An ingestible oral care composition comprising:

2. 10. The ingestible oral care composition of claim 1, further comprising a pH neutralizing agent.

3. 3. The ingestible oral care composition of claim 1 or 2, wherein the polysaccharides and / or derivatives thereof are a combination of arabinogalactan-containing gum, guar gum, xanthan gum, and sodium alginate.

4. 3. The ingestible oral care composition of claim 1 or 2, wherein the polysaccharides and / or derivatives thereof are a combination of gum arabic, pectin, guar gum, xanthan gum, and sodium alginate.

5. 3. The ingestible oral care composition of claim 1 or 2, wherein the polysaccharides and / or derivatives thereof are a combination of gum arabic, guar gum, xanthan gum and sodium alginate.

6. 4. The ingestible oral care composition of claim 3, wherein the arabinogalactan-containing gum is present in an amount of about 0.1% to about 30% by weight; the guar gum is present in an amount of about 0.05% to about 1% by weight; the xanthan gum is present in an amount of about 0.05% to about 1% by weight; and the sodium alginate is present in an amount of about 0.1% to about 10% by weight, based on the total weight of the ingestible oral care composition.

7. 7. The ingestible oral care composition of claim 6, wherein the arabinogalactan-containing gum is gum arabic and is present in an amount of about 1% to about 20% by weight, based on the total weight of the ingestible oral care composition; the guar gum is present in an amount of about 0.05% to about 0.5% by weight, based on the total weight of the ingestible oral care composition; the xanthan gum is present in an amount of about 0.05% to about 0.5% by weight; and the sodium alginate is present in an amount of about 0.5% to about 6% by weight, based on the total weight of the ingestible oral care composition.

8. 8. The ingestible oral care composition of claim 1, wherein the protein is gelatin, hydrolyzed collagen, pea protein, soy protein, rice protein, whey protein, or a combination thereof.

9. 9. The ingestible oral care composition of claim 1, wherein the protein is a combination of hydrolyzed collagen and gelatin.

10. 10. The ingestible oral care composition of claim 9, wherein the protein is present in an amount of about 0.05% to about 10% by weight, based on the total weight of the ingestible oral care composition.

11. 9. The ingestible oral care composition of claim 1, wherein the protein is gelatin.

12. 12. The ingestible oral care composition of claim 11, wherein the gelatin is present in an amount of about 0.1% to about 5% by weight, based on the total weight of the ingestible oral care composition.

13. 13. The ingestible oral care composition of any one of claims 1 to 12, wherein the lipid is a medium chain triglyceride, grapeseed oil, flaxseed oil, avocado oil, coconut oil, palm oil, sunflower oil, olive oil, sesame oil, or a combination thereof.

14. 14. The ingestible oral care composition of claim 13, wherein the lipid is present in an amount of about 0.2% to about 27% by weight, based on the total weight of the ingestible oral care composition.

15. 13. The ingestible oral care composition of any one of claims 1 to 12, wherein the lipid is caprylic / capric triglyceride.

16. 16. The ingestible oral care composition of claim 15, wherein the caprylic / capric triglyceride is present in an amount of about 1% to about 10% by weight, based on the total weight of the ingestible oral care composition.

17. 17. The ingestible oral care composition of any one of claims 2 to 16, wherein the pH neutralizing agent is dicalcium phosphate anhydrous, dicalcium phosphate dihydrate, tricalcium phosphate, or a combination thereof.

18. 20. The ingestible oral care composition of claim 17, wherein the pH neutralizing agent is present in an amount of about 0.2% to about 3% by weight, based on the total weight of the ingestible oral care composition.

19. 19. The ingestible oral care composition of any one of claims 1 to 18, wherein the ingestible oral care composition comprises the active agent.

20. 20. The ingestible oral care composition of claim 19, wherein the active agent comprises a vitamin.

21. 21. The ingestible oral care composition of claim 20, wherein the vitamin is a combination of vitamin C and vitamin B12.

22. 20. The ingestible oral care composition of claim 19, wherein the active material comprises a botanical extract.

23. 20. The ingestible oral care composition of claim 19, wherein the active material comprises an essential oil.

24. 20. The ingestible oral care composition of claim 19, wherein the active agent comprises a pharmaceutically active compound, a vitamin, a botanical extract, an essential oil, or a combination thereof.

25. 20. The ingestible oral care composition of claim 19, wherein the active agent comprises a pharmaceutically active compound.

26. 26. Use of the ingestible oral care composition of any one of claims 1 to 25 to control gingival inflammation in a subject.

27. 26. Use of the ingestible oral care composition of claim 24 or claim 25 to control respiratory disease through the mouth and throat in a subject.

28. 26. Use of the ingestible oral care composition of any one of claims 1 to 25 to prevent systemic diseases associated with periodontal inflammation in a subject.

29. 26. Use of the ingestible oral care composition of any one of claims 1 to 25 to non-invasively destabilize plaque, prevent plaque regrowth and / or reduce plaque on the oral surfaces of a subject.

30. 26. Use of the ingestible oral care composition of any one of claims 19 to 25 to deliver an active agent to a subject in need thereof.

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